The present invention relates to a method of treating a premature neonatal infant with a systemic therapeutic agent transdermally through the intact skin of the infant.
The normal methods of administering systemically active therapeutic agents to preterm infants have distinct drawbacks. Oral administration of such agents generally leads to unpredictable absorption from the undeveloped gastrointestinal tract. Intravenous administration generally requires an access line which has a large dead volume compared with the generally small volume required by the patient. Moreover, the rather fragile and tiny vein size further introduces complications in attempts to administer drugs intravenously in such infants. Further, in preterm infants, inherent dangers are introduced due to the generally narrow therapeutic index of many neonatal therapeutic agents.
The main factor governing percutaneous absorption of an active agent is the permeability barrier function of the skin. However, in premature neonates, the stratum corneum is poorly developed. As a result, the skin of the preterm infant is extremely permeable. Thus, for example, systemically toxic agents applied to the skin of neonates has been reported to result in accidental illness and death. See for example, H. Powell et al., "Hexachlorophene Myelinopathy in Premature Infants", J. Pediatrics, Vol. 82, pp. 976-981 (1973); B. M. Kagan et al, "Cyanosis in Premature Infants Due to Aniline Dye Intoxication", J. Pediatrics, Vol. 34, p. 574-578 (1949).
Attempts have been made to deliver a systemic active agent, theophylline in the form of the sodium glycinate salt, to premature neonatal infants by the use of an hydroxymethylcellulose gel placed on the neonate abdominal skin over a 2 cm.sup.2 diameter area under an occlusive patch. However, in all cases removal of the patch was reported as necessary due to leakage of the gel after 48 hours. See J. Hadgraft et al, "Transdermal Drug Delivery to the Neonate", Proceed. Intern. Symp. Control. Rel. Bioact. Mater., Vol. 12, pp. 349-350 (1985).
It is therefore an object of the present invention to provide a method of administering a systemically active agent which overcomes many of the drawbacks associated with the aformentioned techniques. More specifically, it is an object of the present invention to use the extremely permeable nature of the preterm neonate to transdermally deliver pharmaceutically acceptable systemically active agents to the neonate through intact skin while avoiding the drawbacks associated with a flowable gel.
It is a further object of the invention to provide a transdermal device for use in such a method.
These and other objects of the present invention are apparent from the following specific disclosures.